This invention generally relates to an apparatus and a method for mass producing monodisperse microspheres including therein biodegradable polymers.
Pharmaceutical and bio-medical companies, in response to constant pressure to launch new products onto the market, are spending billions of dollars annually on developing ever more complex and sophisticated therapeutics. However, it is widely acknowledged that many of those therapeutics never reach the market. Even the most promising compound can fail clinical trials if unfavorable pharmacokinetics or poor delivery prevents it from reaching its site of action. Controlling the particulate characteristics of a drug formulation is an increasingly important consideration in pharmaceutical manufacturing, for it can improve a compound's probability of success by improving availability and reducing dosing.
For companies active in biological research, precise control over particle characteristics enables development of novel and sophisticated therapies with advanced drug-delivery systems, and one of such advanced drug-delivery systems currently being actively researched, developed and utilized is so called polymeric drug-delivery system (DDS), capable of, through the use of biodegradable, biocompatible and non-toxic polymers, such as, e.g., polylactic acid (PLA)/polyglycolic (PGA), providing a controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic therapeutic agents (see FIG. 1).
One of the most well-known and representative medical products utilizing the polymeric drug-delivery system is Ellanse™ M from Aqutis/Sinclair, a medical product for tissue regeneration purposes. The product, i.e., Ellanse™ M, includes of monodisperse biocompatible and biodegradable polymeric microspheres, PLA being the active ingredient thereof, and as a consequence of the polymer, i.e., PLA, biodegrading over 2 year period, the tissue generation (or restoration or augmentation) effects of the product end up lasting over the same period of time, provided that the polymeric microspheres in the product are approximately of the same size, i.e., monodispersed.
The most widely used methods for a mass production of polymeric DDS, include phase separation, spray drying and solvent extraction-evaporation, as in the case of mass production of Ellanse™ M. It is, however, almost impossible to control the size of the polymeric microspheres using these processes, resulting in a wide particle size distribution, i.e., polydisperse. Since the optimum desired results of the product can be attained through a narrow microsphere size distribution or monodispersed, those microspheres of undesired sized, therefore, should be removed though a separate process, e.g., filtering, which, in turn, ends up, in addition to increasing the processing time, detrimentally affecting the final yield thereof.